Monoketo enone curcuminoids the treatment of schistosomiasis: an pre-clinical evaluation of schistosomicidal activity

• Grant number: 16/24456-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2017
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Lizandra Guidi Magalhães
• Grantee: Lizandra Guidi Magalhães
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
• Associated researchers: Ana Júlia Pinto Fonseca Sieuve Afonso ; Antônio Eduardo Miller Crotti ; Conor Caffrey ; Denise Crispim Tavares ; Mirela Inês de Sairre ; Renato Luis Tame Parreira ; Silmara Marques Allegretti ; Vladimir Constantino Gomes Heleno
• Associated research grant(s): 18/50011-2 - Exploring turmeric curcuminoids to treat schistosomiasis: an evaluation of their pre-clinical potential, AP.R SPRINT

Abstract

According to the World Health Organization, more than 200 million people are infected with schistosomiasis, most of them in African countries. Schistosomiasis control programs are based mainly on chemotherapy, which is almost limited to praziquantel (PZQ). However, due to the widespread and intensive use of praziquantel, there is an increasing concern about the development of drug-resistant strains. In order to provide new hit/lead structures, which can be used in drug development to control schistosomiasis, the search for antiparasitic compounds from natural sources, mainly from plants, has been intensified in the last years. Studies have been shown that curcumin, a biologically active compound extracted from rhizomes of Curcuma longa, shows schistosomicidal activity in vitro and in vivo. However, curcumin has poor absorption, biodistribution, metabolism, and bioavailability. Thus, studies have been shown that monoketo enone curcuminoids analogs have effects leishmanicidal and trypanocida. Thus, this research project aim is pre-clinical and toxicological evaluation for the development of prototypes drugs for treating of schistosomiasis mansonica. Thus the compounds will be tested at the Center for Discovery and Innovation in Parasitic Diseases (University of California, San Diego) against schistosomula in vitro using a high-content imaging. After, the compounds that have shown a Lethal Concentration (LC50) 10µM will be re-evaluated on juvenile and adult S. mansoni Puerto Rican isolated. In parallel the compounds will be evaluated in vitro on juvenile and adult worms S. mansoni LE (Luiz Evangelista strain) at the University of Franca. The compounds that have shown a LC50 10µM against S. mansoni will be evaluated in vitro on juvenile and adult worms S. mansoni Belo Horizonte (BH), Sergipe (SE), São José dos Campos (SJ) and Belo Horizonte-PZQ resistant (BH-resistant). Additionally, the mechanism of actions and cytotoxicity on mammalian cells also will be evaluated in in vitro for the active compounds. Beside, a possible class effects and structure-activity relationships will be discussed. Based on in vitro performance active compounds will be assayed regarding toxicity for mammalian experimental animals, as well as their therapeutic potential in experimental models of schistosomiasis. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SOUZA, RITIERES LOVO; GONCALVES, UBIRAJARA OLIVEIRA; BADOCO, FERNANDA RAFACHO; GALVAO, LUCAS DE SOUZA; DOS SANTOS, RAQUEL ALVES; DIAS DE CARVALHO, PAULO HENRIQUE; ALEIXO DE CARVALHO, LARA SOARES; DA SILVA FILHO, ADEMAR ALVES; SOLA VENEZIANI, RODRIGO CASSIO; RODRIGUES, VANDERLEI; et al. Licochalcone A induces morphological and biochemical alterations in Schistosoma mansoni adult worms. BIOMEDICINE & PHARMACOTHERAPY, v. 96, p. 64-71, DEC 2017. (15/01394-8, 16/24456-1, 13/11164-4)

DA ROCHA PISSURNO, ANA PAULA; SANTOS, FERNANDA AMORIM; BOLELA BOVO CANDIDO, ANA CAROLINA; MAGALHAES, LIZANDRA GUIDI; DE LAURENTIZ, ROSANGELA DA SILVA. In vitro leishmanicidal activity of lactone 1,4-dihydroquinoline derivatives against Leishmania (Leishmania) amazonensis. MEDICINAL CHEMISTRY RESEARCH, v. 27, n. 9, p. 2224-2229, SEP 2018. (14/07493-5, 16/24456-1, 15/01394-8)

MATOS, JAQUELINE L.; DA SILVA, KAREN R.; DE LIMA PAULA, LUCAS A.; CUNHA, WILSON R.; RAMOS, SALVADOR B.; RODRIGUES, VANDERLEI; CABRAL, FERNANDA J.; MAGALHAES, LIZANDRA G.. Molluscicidal and cercaricidal activities of curcumin on Biomphalaria glabrata and Schistosoma mansoni cercariae. Pest Management Science, v. 76, n. 4, p. 7-pg., 2019-11-08. (13/11164-4, 16/24456-1)

MATOS, JAQUELINE L.; DA SILVA, KAREN R.; DE LIMA PAULA, LUCAS A.; CUNHA, WILSON R.; RAMOS, SALVADOR B.; RODRIGUES, VANDERLEI; CABRAL, FERNANDA J.; MAGALHAES, LIZANDRA G.. Molluscicidal and cercaricidal activities of curcumin on Biomphalaria glabrata and Schistosoma mansoni cercariae. Pest Management Science, NOV 2019. (13/11164-4, 16/24456-1)

VIGATO, ARYANE ALVES; QUEROBINO, SAMYR MACHADO; DE FARIA, NAIALLY CARDOSO; BOLELA BOVO CANDIDO, ANA CAROLINA; MAGALHAES, LIZANDRA GUIDI; SAIA CEREDA, CINTIA MARIA; TOFOLI, GIOVANA RADOMILLE; RAMOS CAMPOS, ESTEFANIA VANGELIE; MACHADO, IAN POMPERMAYER; FRACETO, LEONARDO FERNANDES; et al. Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery. FRONTIERS IN PHARMACOLOGY, v. 10, SEP 12 2019. (18/04036-3, 16/24456-1, 16/18045-9, 18/02482-6, 14/14457-5)

SOUZA, JULIA M.; DE CARVALHO, ERICA A. A.; CANDIDO, ANA CAROLINA B. B.; DE MENDONCA, RAFAEL P.; FERNANDA DA SILVA, MARIA; PARREIRA, RENATO L. T.; DIAS, FERNANDA G. G.; AMBROSIO, SERGIO R.; ARANTES, ANDREA T.; DA SILVA FILHO, ADEMAR A.; et al. Licochalcone a Exhibits Leishmanicidal Activity in vitro and in Experimental Model of Leishmania (Leishmania) Infantum. FRONTIERS IN VETERINARY SCIENCE, v. 7, DEC 10 2020. (13/11164-4, 16/18045-9, 16/24456-1)

BONATTINI, VINICIUS H.; PAULA, LUCAS A. L.; JESUS, NATANA A. M.; CRISPIM, DENISE; NICOLELLA, HELOIZA D.; MAGALHAES, LIZANDRA GUIDI; MOLINA, EDUARDO F.. One-step formation of polyurea gel as a multifunctional approach for biological and environmental applications. Polymer International, v. 69, n. 5, FEB 2020. (13/20455-2, 16/24456-1, 16/16804-0)

DIAS, HERBERT J.; PATROCINIO, ANDRESSA B.; PAGOTTI, MARIANA C.; FUKUI, MURILO J.; RODRIGUES, VANDERLEI; MAGALHAES, LIZANDRA G.; CROTTI, ANTONIO E. M.. Schistosomicidal Activity of Dihydrobenzofuran Neolignans. CHEMISTRY & BIODIVERSITY, v. 15, n. 7, JUL 2018. (13/20094-0, 09/12202-1, 13/11164-4, 16/24456-1, 14/50265-3)

BADOCO, FERNANDA R.; PAULA, LUCAS A. L.; ORENHA, RENATO P.; MENDES, TIAGO M. F.; SQUARISI, IARA S.; EL-SAKKARY, NELLY; LOIOLA, MESSIAS C.; KATZ, NAFTALE; TAVARES, DENISE C.; SAIRRE, MIRELA I.; et al. EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities. Chemico-Biological Interactions, v. 368, p. 11-pg., 2022-10-13. (17/24856-2, 18/50011-2, 15/01394-8, 14/02018-7, 16/18045-9, 16/24456-1)

FRANCISCO, KAROL R.; MONTI, LUDOVICA; YANG, WENQIAN; PARK, HAYOUNG; LIU, LAWRENCE J.; WATKINS, KAITLYN; AMARASINGHE, DILINI K.; NALLI, MARIANNA; POLAQUINI, CARLOS ROBERTO; REGASINI, LUIS O.; et al. Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei. Bioorganic & Medicinal Chemistry Letters, v. 81, p. 9-pg., 2023-01-25. (16/24456-1, 18/50011-2)